Parameter Estimation for Superimposed Weighted Exponentials

The approach of modeling measured signals as superimposed exponentials in white Gaussian noise is popular and effective. However, estimating the parameters of the assumed model is challenging, especially when the data record length is short, the signal strength is low, or the parameters are closely spaced. In this dissertation, we first review the most effective parameter estimation scheme for the superimposed exponential model: maximum likelihood. We then provide a historical review of the linear prediction approach to parameter estimation for the same model. After identifying the improvements made to linear prediction and demonstrating their weaknesses, we introduce a completely tractable and statistically sound modification to linear prediction that we call iterative generalized least squares. It is shown, that our algorithm works to minimize the exact maximum likelihood cost function for the superimposed exponential problem and is therefore, equivalent to the previously developed maximum likelihood approach. However, our algorithm is indeed linear prediction, and thus revives a methodology previously categorized as inferior to maximum likelihood. With our modification, the insight provided by linear prediction can be carried to actual applications. We demonstrate this by developing an effective algorithm for deep level transient spectroscopy analysis. The signal of deep level transient spectroscopy is not a straight forward superposition of exponentials. However, with our methodology, an estimator, based on the exact maximum likelihood cost function for the actual signal, is quickly derived. At the end of the dissertation, we verify that our estimator extends the current capabilities of deep level transient spectroscopy analysis

The effects of irradiation on the biological and biomechanical properties of an acellular porcine superflexor tendon graft for cruciate ligament repair

Acellular xenogeneic tissues have the potential to provide ‘off‐the‐shelf’ grafts for anterior cruciate ligament (ACL) repair. To ensure that such grafts are sterile following packaging, it is desirable to use terminal sterilization methods. Here, the effects of gamma and electron beam irradiation on the biological and biomechanical properties of a previously developed acellular porcine superflexor tendon (pSFT) were investigated. Irradiation following treatment with peracetic acid was compared to peracetic acid treatment alone and the stability of grafts following long‐term storage assessed. Irradiation did not affect total collagen content or biocompatibility (determined using a contact cytotoxicity assay) of the grafts, but slightly increased the amount of denatured collagen in and decreased the thermal denaturation temperature of the tissue in a dose dependant fashion. Biomechanical properties of the grafts were altered by irradiation (reduced ultimate tensile strength and Young's modulus, increased failure strain), but remained superior to reported properties of the native human ACL. Long term storage at 4°C had no negative effects on the grafts. Of all the conditions tested, a dose of minimum 25 kGy of gamma irradiation had least effect on the grafts, suggesting that this dose produces a biocompatible pSFT graft with adequate mechanical properties for ACL repair

Decellularization and Characterization of Porcine Superflexor Tendon: A Potential Anterior Cruciate Ligament Replacement

The porcine superflexor tendon (SFT) was identified as having appropriate structure and properties for development of a decellularised device for use in ACL reconstruction. SFTs were decellularised using a combination of freeze thaw and washes in hypotonic buffer and 0.1% (w/v) SDS in hypotonic buffer plus proteinase inhibitors followed by nuclease treatment and sterilisation using peracetic acid. The decellularised biological scaffold was devoid of cells and cell remnants and contained only 13 ng.mg-1 (dry weight) residual total DNA. Immunohistochemistry showed retention of collagens type I and III and tenascin-C. Quantitative analysis of sulphated sugar and hydroxyproline content revealed a loss of glycosaminoglycans compared to native tissue but no loss of collagen. The decellularised SFT was biocompatible in vitro and in vivo following implantation in a mouse subcutaneous model for 12 weeks. Uniaxial tensile testing to failure indicated that the gross material properties of decellularised SFT were not significantly different to native tissue. Decellularised SFTs had an ultimate tensile strength of 61.8 ± 10.3 MPa (± 95 % confidence limits), a failure strain of 0.29 ± 0.04 and a Young’s modulus of the collagen phase of 294.1 ± 61.9 MPa. Analysis of the presence of the alpha-Gal (galactose-α-1,3-galactose) epitope by immunohistochemistry, lectin binding and antibody absorption assay indicated that the epitope was reduced but still present post decellularisation. This is discussed in light of the potential role of non-cellular alpha-Gal in the acceleration of wound healing and tissue regeneration in the presence of antibodies to alpha-Gal

Decellularisation affects the strain rate dependent and dynamic mechanical properties of a xenogeneic tendon intended for anterior cruciate ligament replacement

Development of new replacement grafts for anterior cruciate ligament (ACL) repair requires mechanical testing to ensure they can provide joint stability following implantation. A decellularised porcine superflexor tendon (pSFT) has been developed previously as an alternative to current reconstruction methods and subjected to biomechanical analysis. The application of varied strain rates to biological tissues is known to alter their biomechanical properties, however the effects of decellularisation on strain rate dependent and dynamic mechanical behaviour of tissues have not been explored. This study utilised tensile testing to investigate the material properties of native and decellularised pSFTs at three different strain rates (1%.s−1, 10%.s−1 and 100%.s−1). In addition, dynamic mechanical analysis (DMA) was used to ascertain the relative contributions of the solid and fluid phase components of the tissues. Ultimate tensile strength was significantly reduced in decellularised compared with native untreated pSFTs but was unaffected by strain rate. In contrast, toe region moduli increased with increasing strain rate for native tissues, but this effect was not observed in decellularised pSFTs. Linear region moduli were unaffected by strain rate, but were significantly reduced in decellularised pSFT compared with native tissue. Following DMA, significant reductions in dynamic modulus, storage modulus and loss modulus were seen in decellularised compared with native pSFT. Interestingly, the damping ability of the tendons was unaffected by decellularisation, suggesting that solid and fluid phases of the tissue were affected equally. These results, alongside previous studies, suggest that decellularisation affects collagen crimp, tissue swelling and collagen fibre sliding. However, despite these findings, the biomechanical properties of decellularised pSFT remain sufficient to act as an off-the-shelf solution for ACL reconstruction

Stratifying the mechanical performance of a decellularized xenogeneic tendon graft for anterior cruciate ligament reconstruction as a function of graft diameter

Objectives: This study investigated the biomechanical performance of decellularized porcine superflexor tendon (pSFT) grafts of varying diameters when utilized in conjunction with contemporary ACL graft fixation systems. This aimed to produce a range of ‘off-the-shelf’ products with predictable mechanical performance, depending on the individual requirements of the patient. Methods: Decellularized pSFTs were prepared to create double-bundle grafts of 7 mm, 8 mm, and 9 mm diameter. Femoral and tibial fixation systems were simulated utilizing Arthrex suspension devices and interference screws in bovine bone, respectively. Dynamic stiffness and creep were measured, followed by ramp to failure from which linear stiffness and load at failure were measured. The mechanisms of failure were also recorded. Results: Dynamic stiffness was found to increase with greater graft diameter, with significant differences between all groups. Conversely, dynamic creep reduced with increasing graft diameter with significant differences between the 7 mm and 9 mm groups and the 8 mm and 9 mm groups. Significant differences were also found between the 7 mm, 8 mm, and 9 mm groups for linear stiffness, but no significant differences were found between groups for load at failure. The distribution of failure mechanisms was found to change with graft diameter. Conclusion: This study showed that decellularized pSFTs demonstrate comparable biomechanical properties to other ACL graft options and are a potentially viable option for ACL reconstruction. Although grafts can be stratified by their diameter to provide varying biomechanical properties, it may be more appropriate to alter the fixation technique to stratify for a greater diversity of biomechanical requirements

Integration and functional performance of a decellularised porcine superflexor tendon graft in an ovine model of anterior cruciate ligament reconstruction

The objective was to evaluate the performance of decellularised porcine superflexor tendon (pSFT) as an anterior cruciate ligament (ACL) reconstruction device. The ACL of adult sheep was reconstructed with decellularised pSFT or ovine allograft SFT and animals sacrificed at 4, 12 and 26 weeks (n = 4 per group) for biological evaluation and 26 weeks (n = 6) for biomechanical evaluation of the grafts. Both grafts showed good in vivo performance with no major differences at macroscopic evaluation post euthanasia. Histopathology revealed an inflammatory reaction to both grafts at 4 weeks, which reduced by 26 weeks. There was advanced cellular ingrowth from 12 weeks, ligamentisation of intra-articular grafts, ossification and formation of Sharpey's fibers at the graft/bone junctions. Immunohistochemistry showed that at 4 and 12 weeks, the host response was dominated by CD163+ M2 macrophages and a cell infiltrate comprising α-SMA + myofibroblasts, CD34+ and CD271+ progenitor cells. At 26 weeks the biomechanical properties of decellularised pSFT and oSFT grafts were comparable, with all grafts failing in the intra-articular region. This study provides new insight into constructive remodelling of tendons used for ACL replacement and evidence of integration and functional performance of a decellularised xenogeneic tendon with potential as an alternative for ACL reconstruction

Decellularised human bone allograft from different anatomical sites as a basis for functionally stratified repair material for bone defects

Tissue engineered bone solutions aim to overcome the limitations of autologous and allogeneic grafts. Decellularised tissues are produced by washing cellular components from human or animal tissue to produce an immunologically safe and biocompatible scaffold, capable of integration following implantation. A decellularisation procedure utilising low concentration sodium dodecyl sulphate (0.1% w/v) was applied to trabecular bone from human femoral heads (FH) and tibial plateaus (TP). Biological (histology, DNA quantification), biomechanical (compression testing) and structural (μCT) comparisons were made between decellularised and unprocessed cellular tissue. Total DNA levels of decellularised FH and TP bone were below 50 ng mg-1 dry tissue weight and nuclear material was removed. No differences were found between cellular and decellularised bone, from each anatomical region, for all the biomechanical and structural parameters investigated. Differences were found between cellular FH and TP and between decellularised FH and TP. Decellularised FH had a higher ultimate compressive stress, Young's modulus and 0.2% proof stress than decellularised TP (p = 0.001, 0.002, 0.001, Mann Whitney U test, MWU). The mineral density of cellular and decellularised TP bone was significantly greater than cellular and decellularised FH bone respectively (cellular: p = 0.001, decellularised: p < 0.001, MWU). The bone volume fraction and trabecular thickness of cellular and decellularised FH bone were significantly greater than cellular and decellularised TP bone respectively (cellular: p = 0.001, 0.005; decellularised: p < 0.001, <0.001, MWU). Characterisation of decellularised trabecular bone from different anatomical regions offers the possibility of product stratification, allowing selection of biomechanical properties to match particular anatomical regions undergoing bone graft procedures

Impacts of bromine and iodine chemistry on tropospheric OH and HO2 : Comparing observations with box and global model perspectives

The chemistry of the halogen species bromine and iodine has a range of impacts on tropospheric composition, and can affect oxidising capacity in a number of ways. However, recent studies disagree on the overall sign of the impacts of halogens on the oxidising capacity of the troposphere. We present simulations of OH and HO2 radicals for comparison with observations made in the remote tropical ocean boundary layer during the Seasonal Oxidant Study at the Cape Verde Atmospheric Observatory in 2009. We use both a constrained box model, using detailed chemistry derived from the Master Chemical Mechanism (v3.2), and the three-dimensional global chemistry transport model GEOS-Chem. Both model approaches reproduce the diurnal trends in OH and HO2. Absolute observed concentrations are well reproduced by the box model but are overpredicted by the global model, potentially owing to incomplete consideration of oceanic sourced radical sinks. The two models, however, differ in the impacts of halogen chemistry. In the box model, halogen chemistry acts to increase OH concentrations (by 9.8% at midday at the Cape Verde Atmospheric Observatory), while the global model exhibits a small increase in OH at the Cape Verde Atmospheric Observatory (by 0.6% at midday) but overall shows a decrease in the global annual mass-weighted mean OH of 4.5%. These differences reflect the variety of timescales through which the halogens impact the chemical system. On short timescales, photolysis of HOBr and HOI, produced by reactions of HO2 with BrO and IO, respectively, increases the OH concentration. On longer timescales, halogen-catalysed ozone destruction cycles lead to lower primary production of OH radicals through ozone photolysis, and thus to lower OH concentrations. The global model includes more of the longer timescale responses than the constrained box model, and overall the global impact of the longer timescale response (reduced primary production due to lower O3 concentrations) overwhelms the shorter timescale response (enhanced cycling from HO2 to OH), and thus the global OH concentration decreases. The Earth system contains many such responses on a large range of timescales. This work highlights the care that needs to be taken to understand the full impact of any one process on the system as a whole

Rare coding SNP in DZIP1 gene associated with late-onset sporadic Parkinson's disease

We present the first application of the hypothesis-rich mathematical theory to genome-wide association data. The Hamza et al. late-onset sporadic Parkinson's disease genome-wide association study dataset was analyzed. We found a rare, coding, non-synonymous SNP variant in the gene DZIP1 that confers increased susceptibility to Parkinson's disease. The association of DZIP1 with Parkinson's disease is consistent with a Parkinson's disease stem-cell ageing theory.Comment: 14 page

Looking ‘beyond the factory gates’:towards more pluralist and radical approaches to intra-organizational trust research

The aim of this paper is to suggest new avenues for trust research by critiquing the extant literature on this topic. We analyze the most influential research on intra-organizational trust from the perspective of a classic industrial sociology framework from the 1970s – Alan Fox’s work on frames of reference and trust dynamics. Our analysis of intra-organizational trust studies leads us to three conclusions. Firstly, the large majority of intra-organizational trust research has strong unitarist underpinnings, which support a managerial agenda that is potentially detrimental to employees’ and (indeed managers’) long-term interests. Secondly, most of this research fails to explain how trust in organizations is embedded in societal and field level institutions, hence it would benefit from looking ‘beyond the factory gates’ for a more complete understanding of trust dynamics in organizations. In this connection, we argue that Fox’s pluralist and radical perspectives, which are under-represented in intra-organizational trust research, could provide new lines of inquiry by locating internal trust relations in a wider institutional context. Thirdly, Fox’s explanation of how low and high trust dynamics in organizations are embedded in wider society may help address the concerns about under-socialized, endogenous explanations and open the way for structure-agency analyses of building, maintaining and repairing intra-organizational trust